高脂饮食可保护阿尔茨海默氏病小鼠模型的血脑屏障,Aging Cell

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高脂饮食可保护阿尔茨海默氏病小鼠模型的血脑屏障
Aging Cell ( IF 8.0 ) Pub Date : 2018-08-06 , DOI: 10.1111/acel.12818
Shirin Elhaik Goldman _{1,

2} , David Goez ₃ , David Last ₃ , Sharone Naor ₁ , Sigal Liraz Zaltsman _{1,

4} , Inbal Sharvit-Ginon _{1,

5} , Dana Atrakchi-Baranes ₁ , Chen Shemesh ₁ , Rachel Twitto-Greenberg _{1,

6} , Shoval Tsach ₁ , Roni Lotan ₁ , Alicia Leikin-Frenkel _{6,

7} , Aviv Shish ₆ , Yael Mardor _{3,

7} , Michal Schnaider Beeri _{1,

8,

9} , Itzik Cooper _{1,

9}

Affiliation

2型糖尿病（T2D）与阿尔茨海默氏病（AD）的风险增加有关。有证据表明这两种疾病的血脑屏障（BBB）受损，但在两者之间相互作用中的作用尚不清楚。在这里，我们就BBB功能研究了高脂饮食（HFD）（一种T2D模型）对AD Tg2576小鼠模型的影响。我们显示，HFD小鼠具有更高的体重，更多的胰岛素抵抗和更高的血清HDL胆固醇水平，主要存在于Tg2576小鼠中，而Tg2576小鼠的脑脂质含量也更高。在行为方面，与常规饮食中的Tg2576相比，Tg2576 HFD小鼠的活动性较低，更焦虑，但在Morris水迷宫中的学习效果更好。HFD对Tg2576小鼠皮层的淀粉样蛋白1–42的水平没有影响，但会增加海马中胰岛素受体的转录水平。与Tg2576 HFD小鼠相比，常规饮食的Tg2576小鼠在8和12个月时表现出更多的BBB破坏，并伴有较大的侧脑室容积，后者的BBB渗漏和心室容积与野生型（WT）小鼠相似。我们的结果表明，在AD中，HFD可能通过改善BBB功能和脑萎缩而不是淀粉样β水平来促进更好的认知功能。中枢神经系统和周围组织中的脂质代谢以及脑胰岛素信号传导可能是这种保护的基础。HFD可能通过改善BBB功能和脑萎缩而促进更好的认知功能，但不能改善淀粉样β水平。中枢神经系统和周围组织中的脂质代谢以及脑胰岛素信号传导可能是这种保护的基础。HFD可能通过改善BBB功能和脑萎缩而促进更好的认知功能，但不能改善淀粉样β水平。中枢神经系统和周围组织中的脂质代谢以及脑胰岛素信号传导可能是这种保护的基础。

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High‐fat diet protects the blood–brain barrier in an Alzheimer's disease mouse model

Type 2 diabetes (T2D) is associated with increased risk of Alzheimer's disease (AD). There is evidence for impaired blood–brain barrier (BBB) in both diseases, but its role in the interplay between them is not clear. Here, we investigated the effects of high‐fat diet (HFD), a model for T2D, on the Tg2576 mouse model of AD, in regard to BBB function. We showed that HFD mice had higher weight, more insulin resistance, and higher serum HDL cholesterol levels, primarily in Tg2576 mice, which also had higher brain lipids content. In terms of behavior, Tg2576 HFD mice were less active and more anxious, but had better learning in the Morris Water Maze compared to Tg2576 on regular diet. HFD had no effect on the level of amyloid beta 1–42 in the cortex of Tg2576 mice, but increased the transcription level of insulin receptor in the hippocampus. Tg2576 mice on regular diet demonstrated more BBB disruption at 8 and 12 months accompanied by larger lateral ventricles volume in contrast to Tg2576 HFD mice, whose BBB leakage and ventricular volume were similar to wild‐type (WT) mice. Our results suggest that in AD, HFD may promote better cognitive function through improvements of BBB function and of brain atrophy but not of amyloid beta levels. Lipid metabolism in the CNS and peripheral tissues and brain insulin signaling may underlie this protection.

更新日期：2018-08-06

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